Effect of estragole on liver tumors glucocorticoid-mediated induction of liver-specific enzymes, and the activity of transcription factors FOXA and HNF4 in mouse and rat liver

Каледин, В. И.; Pakharukova, Maria Y.; Пивоварова, Е. Н.; Kropachev, Konstantin; Baginskaya, N. V.; Vasilieva, E. D.; Ilnitskaya, S. I.; Nikitenko, E. V.; Кобзев, В. Ф.; Меркулова, Т. И.

doi:10.1134/s0006350910020193

Cited by 2 publications

(1 citation statement)

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“…Recently, elemicin has attracted much attention owing to its extensive pharmacological potential, including antimicrobial, antioxidant, and antiviral activities. However, as an alkenylbenzenes, elemicin is similar to estragole, safrole, methyleugenol and myristicin, that cause genotoxicity and hepatocarcinogenic effects in rodent models. − It was previously revealed that 1′-hydroxylation of alkenylbenzenes could generate electrophilic derivatives such as 1′-hydroxyestragole and 1′-hydroxysafrole. , These metabolites can react with DNA and form genotoxic carcinogens. However, the potential toxicity of elemicin remains unclear. ,, …”

Section: Introductionmentioning

confidence: 99%

Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1

Yang

Wang

Zhu

et al. 2019

Chem. Res. Toxicol.

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Elemicin is a constituent of natural aromatic phenylpropanoids present in many herbs and spices. However, its potential to cause toxicity remains unclear. To examine the potential toxicity and associated mechanism, elemicin was administered to mice for 3 weeks and serum metabolites were examined. Enlarged livers were observed in elemicin-treated mice, which were accompanied by lower ratios of unsaturated- and saturated-lysophosphatidylcholines in plasma, and inhibition of stearoyl-CoA desaturase 1 (Scd1) mRNA expression in liver. Administration of the unsaturated fatty acid oleic acid reduced the toxicity of 1′-hydroxylelemicin, the primary oxidative metabolite of elemicin, while treatment with the SCD1 inhibitor A939572 potentiated its toxicity. Furthermore, the in vitro use of recombinant human CYPs and chemical inhibition of CYPs in human liver microsomes revealed that CYP1A1 and CYP1A2 were the primary CYPs responsible for elemicin bioactivation. Notably, the CYP1A2 inhibitor α-naphthoflavone could attenuate the susceptibility of mice to elemicin-induced hepatomegaly. This study revealed that metabolic activation of elemicin leads to SCD1 inhibition in liver, suggesting that upregulation of SCD1 may serve as potential intervention strategy for elemicin-induced toxicity.

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